Potential Role of Rho Kinase Inhibitors in Combating Diabetes-Related Complications Including Diabetic Neuropathy-A Review

Ram      Kumar Mishra; Reshma      Alokam; Dharmarajan      Sriram; Perumal      Yogeeswari

doi:10.2174/1573399811309030006

Abstract

The worldwide epidemic scale of diabetes mellitus has been underestimated for a long time. Currently every 10 seconds one patient dies of diabetes-related pathologies. Given the high risk and prevalence of secondary complications as well as individual predisposition to target organ injury, diabetes is one of the major risk factors for various organ and tissue dysfunctions including nerves. The present review outlines the role of Rho Kinase (ROCK) in various diabetic indications: diabetic neuropathy, erectile dysfunction, cardiomyopathy, sexual dysfunction, nephropathy, cardiomyopathy, retinopathy, cerebro-vascular disease and cystopathy. We found that ROCK is involved in various pathophysiological mechanisms, leading to a number of unique diabetic complications. Recent studies have indicated an increasing interest in the use of ROCK inhibitors like Y-27632, H1152 and fasudil not only for the treatment of diabetic neuropathy, but also for the treatment of sexual dysfunction, cardiomyopathy and other diabetic complications. The pathophysiological mechanism has been extensively analyzed and the current status of ROCK inhibitors has been discussed in the review.

Keywords: Angiopathy, Cardiomyopathy, Diabetes, Diabetic complications, Erectile dysfunction, Fasudil, H1152, Nephropathy, Neuropathy, Retinopathy, Rho Kinase, Rho kinase inhibitor, ROCK, RhoA, Y27632